AstraZeneca's Cardiovascular Drug: Risks Up, Risks Down

AstraZeneca (AZN) took a pretty big risk in running a trial as big as the JUPITER one, but it seems to have paid off for them. As everyone has been reading, it appears that their Crestor (rosuvastatin) lowers the risk of cardiovascular events in patients with elevated C-reactive protein, even those with reasonable cholesterol numbers (NEJM paper here).

These patients don’t have an awful lot of heart attacks, but they did have less while on the drug. That’s going to be enough, all by itself, to expand the market for Crestor (and probably the other statins as well). The question is whether the others will have the same effect. You’d think so, especially in a similar strong one like Lipitor, but AstraZeneca is the only company with numbers for its own product.

The question will be whether it’s worth treating such a wider patient population at these intent-to-treat numbers, a point made in an accompanying editorial in the New England Journal of Medicine:

The relative risk reductions achieved with the use of statin therapy in JUPITER were clearly significant. However, absolute differences in risk are more clinically important than relative reductions in risk in deciding whether to recommend drug therapy, since the absolute benefits of treatment must be large enough to justify the associated risks and costs. The proportion of participants with hard cardiac events in JUPITER was reduced from 1.8% (157 of 8901 subjects) in the placebo group to 0.9% (83 of the 8901 subjects) in the rosuvastatin group; thus, 120 participants were treated for 1.9 years to prevent one event.

It’s interesting to imagine these numbers flipped over, though – if a drug caused heart attacks at these same statistical levels in these same patients, it would be taken off the market immediately. Look, for example, at the risks of cardiovascular problems with Vioxx. The VIGOR trial showed 17 heart attacks in a group of over 4,000 patients, a rate (at the highest dose) of about four times the naproxen-treated control group. In relative risk terms, that’s a serious alarm bell – but in absolute risk, not so much.

This isn’t a completely fair comparison, of course – in the case of statins, cardiovascular events are what you’re trying to treat in the first place, as opposed to having them as a totally unrelated side effect in a pain medication. And there were other options than a Cox-2 inhibitor for many (although not for all) of the people taking Vioxx. And there’s the general primum non nocere principle: when we find that a drug is causing actual harm (as opposed to doing nothing), it’s likely to be withdrawn, even if the harm is at very low statistical levels.

But at the same time, not giving people something that could prevent these heart attacks is still rather equivalent to causing said heart attacks – isn’t it? We have to make the call of whether the cost, and the statin side effects, are worth it. That’s not an easy one (for one thing, there was a statistically significant difference in the number of Crestor-treated patients showing diabetic symptoms in this trial). And when a drug shows harmful side effects, we should make the call in the same way. I just don’t see the two situations treated in a similar manner much of the time, though.